Both hypertension and diabetes augment and enhance atherosclerosis. The basic strategy of the research program proposed is to take a key feature of atherosclerosis--lipid overloading--and examine how the process is accelerated in the presence of hypertension or diabetes. The research focus is on lipid deposition in cells and whether this process influences the production of bioactive agents by vascular cells, and if so, how it is reflected in the develop- ment of gross lesions. Exacerbation of vascular disease will be followed in both diet-induced and genetic-determined (Watanabe WHHL strain) hypercholesterolemia in rabbits with Goldblatt hypertension. A new model of accelerated atherosclerosis in alloxanized dutch belted rabbits will be used to study the diabetic microvascular disease. The specific aims of the project are: (1) To quantitate by nile red fluorescent staining and digitized imaging, hypertension or diabetes accelerated lipid deposition in atherosclerosis. Surface maps of probability of lesion occurrence in arteries will be generated and correlated with the morphologic features of the lesions. (2) To use flow cytometry, following enzymic isolation of cells, to monitor alterations in vessel wall cell populations in hypercholesterolemia-induced atherosclerosis as a consequence of hypertension or diabetes. These studies will look at the influx of monocytes/macrophages into arterial lesions; the lipid deposition in both macrophages and smooth muscle cells and their transformation into foam cells; and the proliferation of smooth muscle cells and macrophages. (3) To determine by biochemical and recombinant ONA techniques, whether cells isolated from hypertensive or diabetic atherosclerotic arteries more actively elaborate various potent biological agents. The agents to be examined include growth factors, hydrolytic enzymes, and reactive metabolites of oxygen. The data generated will be correlated with digitized images of lesion extent and severity in the vessels from which the cells have been isolated.